Lung Revascularization Reversal Of Experimental Emphysema

Pulmonary emphysema is a common disease severely threatening human health in worldwide.There is still no effective drug to prevent the progressive loss of lung parenchyma at present.According to the available pathogenesy of emophysema,the destruction of the alveolar walls,one of the pathologic changes in pulmonary emphysema,had been considered irreversible. After studied and researched Lung Volume Reduction Surgery(LVRS)and the Bronchial lumen blocking up,Professer Li BaoPing had proposed a new pathogenesy of emphysema:"The damage to the pulmonary capillary plays an important role in the development of pulmonary emphysema.The damages of pulmonary alveolus capillary caused the loss of pulmonary blood flow,lead to ventilates/perfusion shunted,and the lungs reduced the gas diffusion area for compensate the shunt of ventilates/perfusion,by enlarging alveolus.Finally,this led to the appears of pulmonary emphysema".According to the hypothesis,the pathology of emphysema can be was restored by promoting pulmonary capillary regenerated.Study objectives:This research will verify our hypothesis by promoting the pulmonary capillary of elastase-induced emphysema rats in using bFGF,VEGF and MSCs.The study will improve the pathogenesy of emphysema and supply a new approach and theory to the treatment of emphysema.Methods:In the first part,twelve 8 week old Wister rats weighing 180 to 200g were classified at random into the following 2 groups:Model group(A,n=6)and Control group(B, n=6).A group rats received a single intratracheal instillation of porcine pancreatic elastase(PPE) (2U/g).Rats of B group were intratracheal injected Sodium Chloride.4 weeks later,we measured the arterial blood gas and detected alveoli morphology and confirm the pulmonary capillary to appraise the models.In the second part,thirty six 8 week old Wister rats weighing 180 to 200g were classified at random into the following 6 groups:bFGF group(A,n=6),VEGF group(B,n=6),MSCs group(C, n=6),MSC+bFGF group(D,n=6),Control group(E,n=6)and Normal group(F,n=6).A,B,C,D,E group rats received a single intratracheal instillation of PPE respectively.Rats of F group were intratracheal injected Sodium Chloride.4 weeks after PPE administration,the emphysema models succeeded.Then A,B group rats were respectively intratracheal injected bFGF(400U),VEGF(2ug),once a week,3 times in all,and injected Sodium Chloride into tail vein(once);C group rats were injected MSCs labeled with BrdU into tail vein(once)and intratracheal injected Sodium Chloride(3 times);D group rats were injected MSCs labeled with BrdU(once)into tail vein and intratracheal injected bFGF(400U)(3 times);E,F group rats were intratracheal injected Sodium Chloride and injected Sodium Chloride into tail vein;4 weeks after treatment,we measured the arterial blood gas,and detected alveoli morphology for assessment of pulmonary pathological changes.To confirm the pulmonary capillary,immunohistochemistry staining was performed using CD34 to mark the pulmonary capillary endothelial cells,which helps to research the possible mechanism of bFGF and VEGF restored pulmonary emphysema,and the pathogenesy of pulmonary emphysema,in order to provide theoretical foundation for clinical therapy of pulmonary emphysema.Results:1,4 weeks after PPE intratracheal administration,emphysematous rat model similar to human emphysema was successfully induced.The pulmonary capillary was significantly decreased than control group.2,MSCs injected from tail vein was found in the lung.3,bFGF,VEGF and MSC increased pulmonary capillary,and the Mean Alveoli Number (MAN)of treatment group was significantly increased than the control group.Mean Linear intercept(MLI)and Mean Alveoli Area(MAA)was significantly reduced than control group. The number of pulmonary capillary endothelial cells of the bFGF and VEGF and MSCs group was significantly increased than control group.But the change of artery blood gas analysis was not statistically significant after treatment.Conclusion:1,The proliferation of pulmonary capillary improved the pathology of pulmonary emphysema.2,The possibly mechanism ofbFGF and VEGF recovery the pulmonary emphysema is:①the proliferation of pulmonary capillary improved the blood flow of emphysema.These improvements led to an improvement in the ventilation/perfusion shunt and in the gas exchange ability of the lung,the lung can adjust the volume and the size of pulmonary alveolus through own compensation and make the lung volume and pulmonary alveolus become smaller.②The increased blood flow of emphysema improved self-repairing capability of lungs,the typeⅡpenumonocyte restored the emphysame by self-replication and differentiating typeⅠpenumonocyte.3,It verified the hypothesis in some degree,"The damage to the pulmonary capillary plays an important role in the development of pulmonary emphysema."...